3-186853103-T-G

Variant names:

• chr3-186853103-T-G
• rs2241766
• NM_004797.4:c.45T>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_004797.4(ADIPOQ):​c.45T>G​(p.Gly15Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 1,614,010 control chromosomes in the GnomAD database, including 13,827 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.11 (1139 hom., cov: 32)
  • Exomes 𝑓: 0.12 (12688 hom.)
• Consequence: ADIPOQ NM_004797.4 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.387
• Publications: 611 publications found

Genes affected

ADIPOQ (HGNC:13633): (adiponectin, C1Q and collagen domain containing) This gene is expressed in adipose tissue exclusively. It encodes a protein with similarity to collagens X and VIII and complement factor C1q. The encoded protein circulates in the plasma and is involved with metabolic and hormonal processes. Mutations in this gene are associated with adiponectin deficiency. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Apr 2010]

ADIPOQ-AS1 (HGNC:40648): (ADIPOQ antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 3-186853103-T-G is Benign according to our data. Variant chr3-186853103-T-G is described in ClinVar as [Benign]. Clinvar id is 3060531.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-0.387 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.281 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADIPOQ	NM_004797.4	c.45T>G	p.Gly15Gly	synonymous_variant	Exon 2 of 3	ENST00000320741.7	NP_004788.1
ADIPOQ	NM_001177800.2	c.45T>G	p.Gly15Gly	synonymous_variant	Exon 3 of 4		NP_001171271.1
ADIPOQ-AS1	NR_046662.2	n.2355A>C		non_coding_transcript_exon_variant	Exon 4 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADIPOQ	ENST00000320741.7	c.45T>G	p.Gly15Gly	synonymous_variant	Exon 2 of 3	1	NM_004797.4	ENSP00000320709.2
ADIPOQ	ENST00000444204.2	c.45T>G	p.Gly15Gly	synonymous_variant	Exon 3 of 4	1		ENSP00000389814.2
ADIPOQ-AS1	ENST00000422718.1	n.2226A>C		non_coding_transcript_exon_variant	Exon 3 of 3	5

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16297 AN: 152042 Hom.: 1141 Cov.: 32

Gnomad AFR AF: 0.0469

Gnomad AMI AF: 0.0735

Gnomad AMR AF: 0.185

Gnomad ASJ AF: 0.207

Gnomad EAS AF: 0.294

Gnomad SAS AF: 0.133

Gnomad FIN AF: 0.0499

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.161

GnomAD2 exomes AF: 0.135 AC: 33830 AN: 251118 AF XY: 0.135

Gnomad AFR exome AF: 0.0427

Gnomad AMR exome AF: 0.187

Gnomad ASJ exome AF: 0.199

Gnomad EAS exome AF: 0.301

Gnomad FIN exome AF: 0.0511

Gnomad NFE exome AF: 0.115

Gnomad OTH exome AF: 0.140

GnomAD4 exome AF: 0.124 AC: 181897 AN: 1461850 Hom.: 12688 Cov.: 32 AF XY: 0.125 AC XY: 90730 AN XY: 727226

African (AFR) AF: 0.0431 AC: 1442 AN: 33480

American (AMR) AF: 0.183 AC: 8183 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.206 AC: 5372 AN: 26134

East Asian (EAS) AF: 0.297 AC: 11770 AN: 39694

South Asian (SAS) AF: 0.128 AC: 11028 AN: 86250

European-Finnish (FIN) AF: 0.0521 AC: 2785 AN: 53418

Middle Eastern (MID) AF: 0.215 AC: 1243 AN: 5768

European-Non Finnish (NFE) AF: 0.118 AC: 131658 AN: 1111988

Other (OTH) AF: 0.139 AC: 8416 AN: 60394

GnomAD4 genome AF: 0.107 AC: 16300 AN: 152160 Hom.: 1139 Cov.: 32 AF XY: 0.109 AC XY: 8131 AN XY: 74388

African (AFR) AF: 0.0469 AC: 1948 AN: 41532

American (AMR) AF: 0.185 AC: 2824 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.207 AC: 717 AN: 3466

East Asian (EAS) AF: 0.293 AC: 1511 AN: 5150

South Asian (SAS) AF: 0.133 AC: 642 AN: 4828

European-Finnish (FIN) AF: 0.0499 AC: 529 AN: 10604

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.112 AC: 7642 AN: 67974

Other (OTH) AF: 0.162 AC: 342 AN: 2112

Alfa AF: 0.114 Hom.: 2231

Bravo AF: 0.115

Asia WGS AF: 0.210 AC: 728 AN: 3478

EpiCase AF: 0.129

EpiControl AF: 0.136

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

ADIPOQ-related disorder Benign:1

Oct 30, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.1
DANN	Benign	0.50
PhyloP100		-0.39
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2241766; hg19: chr3-186570892; COSMIC: COSV57859918;